Chemotherapy: Alkylating Agents

Chemotherapy Drugs

• Chemotherapy drugs target rapidly dividing cells to treat cancer

Alkylating Agents

• Cyclophosphamide causes DNA cross-linking and is non-specific to the cell cycle
  • Route of administration is IV or oral
  • Requires hydration and monitoring for hemorrhagic cystitis
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, alopecia, hemorrhagic cystitis, and cytopenias
  • Dangerous toxicities include secondary malignancy and cardiotoxicity
• Ifosfamide causes DNA cross-linking and is non-specific to the cell cycle
  • Administered intravenously
  • Requires Mesna co-administration and hydration
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, alopecia, hemorrhagic cystitis, and cytopenias
• Melphalan causes DNA alkylation and is non-specific to the cell cycle
  • Administered intravenously or orally
  • Requires monitoring of pulmonary function and hydration
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, cytopenias, and mucositis
  • A dangerous toxicity is pulmonary fibrosis
• Chlorambucil causes DNA alkylation and is non-specific to the cell cycle
  • Administered orally
  • Requires monitoring of blood counts and avoidance of live vaccines
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, fatigue, and cytopenias
  • Dangerous toxicities include secondary malignancy and infertility
• Busulfan causes DNA alkylation and is non-specific to the cell cycle
  • Administered intravenously or orally
  • Requires seizure prophylaxis and monitoring of liver/pulmonary function
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, cytopenias, and mucositis
  • Dangerous toxicities include pulmonary fibrosis, seizures, and VOD
• Dacarbazine causes DNA methylation and is non-specific to the cell cycle
  • Administered intravenously
  • Requires protection from light and monitoring of liver function
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, vomiting, and fatigue
• Temozolomide causes DNA methylation and is non-specific to the cell cycle
  • Administered orally on an empty stomach
  • Requires monitoring of blood counts
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, fatigue, and cytopenias
  • Dangerous toxicities include myelosuppression, hepatotoxicity, and secondary malignancy
• Bendamustine causes DNA cross-linking and acts as a purine analog, non-specific to the cell cycle
  • Administered intravenously
  • Requires monitoring for infusion reactions and infections
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, fatigue, and cytopenias
  • Dangerous toxicities include myelosuppression, infection, and rash
• Procarbazine causes DNA methylation and is non-specific to the cell cycle
  • Administered orally, requires avoidance of tyramine-rich foods, and monitoring of CNS
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, fatigue, and cytopenias
  • Dangerous toxicity includes neurotoxicity
• Thiotepa causes DNA cross-linking and is non-specific to the cell cycle
  • Requires skin monitoring and avoidance of extravasation
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, cytopenias, and mucositis
  • Dangerous toxicities include myelosuppression, skin toxicity, and infection
• Mechlorethamine causes DNA cross-linking and is non-specific to the cell cycle
  • Administered intravenously or topically, requires avoidance of extravasation, and monitoring of skin
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, vomiting, and skin irritation
  • Dangerous toxicities include myelosuppression, skin necrosis, and secondary malignancy
• Altretamine causes DNA damage through an unknown mechanism
  • It is non-specific to the cell cycle
  • Administered orally
  • Requires monitoring of neurotoxicity and blood counts
  • Dose-limiting toxicity is neurotoxicity
  • Common toxicities include nausea, fatigue, and neuropathy
  • Dangerous toxicities include neurotoxicity, myelosuppression, and hepatotoxicity
• Trabectedin binds to the DNA minor groove and is non-specific to the cell cycle
  • Administered intravenously
  • Requires monitoring of liver function and avoidance of extravasation
  • Dose-limiting toxicity is hepatotoxicity
  • Common toxicities include nausea, fatigue, and cytopenias
  • Dangerous toxicities include hepatotoxicity, myelosuppression, and rhabdomyolysis

Platinum Compounds

• Cisplatin causes DNA cross-linking and is non-specific to the cell cycle
  • Requires hydration and monitoring of renal/hearing function
  • Dose-limiting toxicity is nephrotoxicity
  • Common toxicities include nausea, vomiting, nephrotoxicity, neurotoxicity, and ototoxicity
• Carboplatin causes DNA cross-linking and is non-specific to the cell cycle
  • Requires monitoring of renal function and dose adjustment by AUC
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, cytopenias, and fatigue
  • Dangerous toxicities include nephrotoxicity, myelosuppression, and hypersensitivity
• Oxaliplatin causes DNA cross-linking and is non-specific to the cell cycle
  • Requires avoidance of cold exposure
  • Dose-limiting toxicity is neurotoxicity
  • Common toxicities include neuropathy, nausea, and diarrhea
  • Dangerous toxicities include anaphylaxis and liver toxicity

Antimetabolites

• Methotrexate inhibits DHFR (folate synthesis) and is specific to the S phase
  • Requires leucovorin rescue and monitoring of renal function
  • Administered IV, orally, or intrathecally (IT)
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include mucositis, nausea, cytopenias, and pneumonitis
  • Dangerous toxicities include hepatotoxicity, nephrotoxicity, and myelosuppression
• 5-Fluorouracil (5-FU) inhibits thymidylate synthase and is specific to the S phase
  • Requires cardiac risk factor monitoring and monitoring for hand-foot syndrome
  • Administered IV or topically
  • Dose-limiting toxicity is cardiotoxicity
  • Common toxicities include mucositis, diarrhea, myelosuppression, and nausea.
  • Dangerous toxicities include myelosuppression
• Capecitabine converts to 5-FU that inhibits thymidylate synthase and is specific to the S phase
  • Administered orally
  • Requires monitoring for hand-foot syndrome and liver function
  • Dose-limiting toxicity is hand-foot syndrome
  • Common toxicities include diarrhea, nausea, fatigue, and myelosuppression
  • Dangerous toxicities include cardiotoxicity, hepatotoxicity, neurotoxicity, and renal failure
• Gemcitabine incorporates into DNA and inhibits synthesis, specific to the S phase
  • Administered intravenously
  • Requires monitoring of pulmonary function and liver function
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, cytopenias, and fatigue
  • Dangerous toxicity is pulmonary toxicity and hepatotoxicity
• Cytarabine inhibits DNA polymerase and is specific to the S phase
  • Administered IV, subcutaneously (SC), or intrathecally (IT)
  • Requires monitoring for cerebellar toxicity and hydration
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, cytopenias, and mucositis
  • Dangerous toxicity is neurotoxicity
• 6-Mercaptopurine inhibits purine synthesis and is specific to the S phase
  • Administered orally, requires monitoring of liver function and avoidance of allopurinol
  • Dose-limiting toxicity is hepatotoxicity
  • Common toxicities include nausea, cytopenias, and fatigue
  • Dangerous toxicities include hepatotoxicity, myelosuppression, and infection risk
• Fludarabine inhibits DNA synthesis and is specific to the S phase
  • Administered intravenously, requires monitoring for infection and neurotoxicity
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include fever, fatigue, and cytopenias
  • Dangerous toxicities include neurotoxicity, infection, and autoimmune hemolysis
• Cladribine inhibits DNA synthesis and is specific to the S phase
  • Requires monitoring for infection and renal function
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include fatigue, nausea, and cytopenias
  • Dangerous toxicities include infection, neurotoxicity, and myelosuppression
• Pemetrexed inhibits folate-dependent enzymes during the S phase
  • Requires folic acid/B12 supplementation and monitoring of renal function
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include fatigue, nausea, and cytopenias
  • Dangerous toxicities include nephrotoxicity, pneumonitis, and myelosuppression
• Azacitidine causes DNA hypomethylation, non-specific to cell cycle
  • It is specific to the S phase
  • Administered intravenously or subcutaneously
  • Requires monitoring of renal/liver function
  • Dose-limiting toxicity is Myelosuppression
  • Common toxicities are Nausea, cytopenias, fatigue
  • Dangerous toxicities are Myelosuppression, infection, hepatotoxicity
• Decitabine causes DNA hypomethylation, non-specific to cell cycle
  • It is specific to the S phase
  • Administered intravenously
  • Requires monitoring of renal/liver function
  • Dose-limiting toxicity is Myelosuppression
  • Common toxicities are Nausea, cytopenias, fatigue
  • Dangerous toxicities are Myelosuppression, infection, hepatotoxicity
• Hydroxyurea inhibits ribonucleotide reductase and is specific to the S phase
  • Administered orally
  • Requires monitoring of blood counts and renal function
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include fatigue, nausea, and cytopenias
  • Dangerous toxicities include myelosuppression, skin ulcers, and secondary malignancy
• Nelarabine inhibits DNA synthesis and is specific to the S phase
  • Administered intravenously
  • Requires monitoring of neurotoxicity and renal function
  • Dose-limiting toxicity is neurotoxicity
  • Common toxicities include fatigue, cytopenias, and nausea
  • Dangerous toxicities include neurotoxicity, myelosuppression, and infection
• Pentostatin inhibits adenosine deaminase and is specific to the S phase
  • Administered intravenously
  • Requires monitoring of renal function and infection risk
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include fatigue, nausea, and cytopenias
  • Dangerous toxicities include myelosuppression, neurotoxicity, and infection
• Thioguanine inhibits purine synthesis and is specific to the S phase
  • Administered orally
  • Requires monitoring of liver function and blood counts
  • Dose-limiting toxicity is hepatotoxicity
  • Common toxicities include nausea, cytopenias, and fatigue
  • Dangerous toxicities include hepatotoxicity, myelosuppression, and VOD

Anthracyclines

• Doxorubicin intercalates DNA and inhibits topoisomerase II, non-specific to the cell cycle
  • Administered intravenously
  • Requires monitoring of cardiac function and lifetime dose limit
  • Dose-limiting toxicity is cardiotoxicity
  • Common toxicities include nausea, alopecia, and cytopenias
  • Dangerous toxicities include cardiotoxicity, myelosuppression, and secondary malignancy
• Daunorubicin intercalates DNA and inhibits topoisomerase II, non-specific to the cell cycle
  • Administered intravenously
  • Requires monitoring of cardiac function and lifetime dose limit
  • Dose-limiting toxicity is cardiotoxicity
  • Common toxicities include nausea, alopecia, and cytopenias
  • Dangerous toxicities include cardiotoxicity, myelosuppression, and secondary malignancy
• Epirubicin intercalates DNA and inhibits topoisomerase II, non-specific to the cell cycle
  • Administered intravenously
  • Requires monitoring of cardiac function and lifetime dose limit
  • Dose-limiting toxicity is cardiotoxicity
  • Common toxicities include nausea, alopecia, and cytopenias
  • Dangerous toxicities include cardiotoxicity, myelosuppression, and secondary malignancy
• Idarubicin intercalates DNA and inhibits topoisomerase II, non-specific to the cell cycle
  • Administered intravenously
  • Dose-limiting toxicity is cardiotoxicity
  • Common toxicities include nausea, cytopenias, and mucositis
  • Dangerous toxicities include cardiotoxicity, myelosuppression, and secondary malignancy
• Mitoxantrone intercalates DNA and inhibits topoisomerase II and is non-specific to the cell cycle
  • Administered intravenously
  • Requires monitoring of cardiac function and lifetime dose limit
  • Dose-limiting toxicity is cardiotoxicity
  • Common toxicities include nausea, cytopenias, and fatigue
  • Dangerous toxicities include cardiotoxicity, myelosuppression, and secondary malignancy

Antitumor Antibiotics

• Bleomycin causes DNA strand breaks via free radicals and is specific to the G2 and M phases
  • Administered IV, IM, or SC
  • Requires monitoring of pulmonary function and avoidance of high O2
  • Dose-limiting toxicity is pulmonary toxicity
  • Common toxicities include fever, rash, and mucositis
  • Dangerous toxicities include pulmonary fibrosis, anaphylaxis, and hyperpigmentation
• Dactinomycin intercalates DNA and inhibits transcription, non-specific to cell cycle
  • Administered intravenously
  • Requires monitoring of liver function and avoidance of extravasation
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, alopecia and cytopenias
  • Dangerous toxicities include hepatotoxicity, myelosuppression and VOD
• Mitomycin-C causes DNA cross-linking and is non-specific to the cell cycle
  • Administered intravenously
  • Requires monitoring of pulmonary/renal function and avoidance of extravasation
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, cytopenias, and mucositis
  • Dangerous toxicity is pulmonary toxicity, HUS, and myelosuppression

Vinca Alkaloids

• Vincristine inhibits microtubule formation and is specific to the M phase
  • Administered intravenously
  • Requires avoidance of extravasation and monitoring of neurotoxicity
  • Dose-limiting toxicity is neurotoxicity
  • Common toxicities include neuropathy, constipation, and alopecia
  • Dangerous toxicities include neurotoxicity, ileus, and SIADH
• Vinblastine inhibits microtubule formation and is specific to the M phase
  • Administered intravenously
  • Requires avoidance of extravasation and monitoring of neurotoxicity
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include neuropathy, alopecia, and cytopenias
  • Dangerous toxicities include neurotoxicity, myelosuppression, and SIADH
• Vinorelbine inhibits microtubule formation and is specific to the M phase
  • Administered intravenously
  • Requires avoidance of extravasation and monitoring of neurotoxicity
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include neuropathy, nausea, and cytopenias
  • Dangerous toxicity is neurotoxicity, myelosuppression, and constipation

Taxanes

• Paclitaxel stabilizes microtubules and is specific to the M phase
  • Administered intravenously
  • Requires premedication for hypersensitivity and monitoring of neuropathy
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include neuropathy, alopecia, and nausea
  • Dangerous toxicities include hypersensitivity, neurotoxicity, and myelosuppression
• Docetaxel stabilizes microtubules and is specific to the M phase
  • Administered intravenously
  • Requires premedication with steroids and monitoring of fluid retention
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include neuropathy, alopecia, and fluid retention
  • Dangerous toxicities include hypersensitivity, neurotoxicity, and myelosuppression
• Cabazitaxel stabilizes microtubules and is specific to the M phase
  • Administered intravenously
  • Requires premedication for hypersensitivity and monitoring of neutropenia
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, fatigue, and dizziness
  • Dangerous toxicities include myelosuppression, hypersensitivity, and neuropathy

Topoisomerase Inhibitors

• Etoposide inhibits topoisomerase II and is specific to the late S and G2 phases
  • Administered IV or orally
  • Requires monitoring of blood counts and avoidance of rapid infusion
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, alopecia, and cytopenias
  • Dangerous toxicities include myelosuppression, secondary leukemia, and mucositis
• Irinotecan inhibits topoisomerase I and is specific to the S phase
  • Administered intravenously
  • Requires management of diarrhea and monitoring of liver function
  • Dose-limiting toxicity is diarrhea
  • Common toxicities include diarrhea, nausea, and cytopenias
  • Dangerous toxicities include severe diarrhea, myelosuppression, and hepatotoxicity
• Topotecan inhibits topoisomerase I and is specific to the S phase
  • Administered intravenously
  • Requires monitoring of blood counts and renal function
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, cytopenias, and fatigue
  • Dangerous toxicities include myelosuppression, infection, and pneumonitis

Nitrosoureas

• Carmustine alkylates DNA, crosses the blood-brain barrier, and is non-specific to the cell cycle
  • Administered intravenously, requires monitoring of pulmonary function, avoidance of alcohol
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, cytopenias, and fatigue
  • Dangerous toxicities include pulmonary fibrosis, myelosuppression, and secondary malignancy
• Lomustine alkylates DNA, crosses the blood-brain barrier, , and is non-specific to the cell cycle
  • Administered orally
  • Requires monitoring of blood counts and liver function
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include nausea, cytopenias, and fatigue
  • Dangerous toxicities include hepatotoxicity, neurotoxicity, myelosuppression, and secondary malignancy

Other Chemotherapy Drugs

• Asparaginase depletes asparagine, inhibits protein synthesis, and is non-specific to the cell cycle
  • Administered IV or IM
  • Requires monitoring of coagulation and allergic reactions
  • Dose-limiting toxicity is coagulopathy
  • Common toxicities include nausea, fever, and hypersensitivity
  • Dangerous toxicities include hypersensitivity, thrombosis, and pancreatitis
• Tretinoin (ATRA) induces differentiation and is non-specific to the cell cycle
  • Administered orally
  • Requires monitoring of retinoic acid syndrome and liver function
  • Dose-limiting toxicity is retoinoic acid syndrome
  • Common toxicities include headache, rash, and dry skin
  • Dangerous toxicities include retinoic acid syndrome, hepatotoxicity, and pseudotumor cerebri
• Arsenic Trioxide induces apoptosis and degrades PML-RARα and is non-specific to the cell cycle
  • Administered intravenously, requires monitoring of QT interval and electrolytes
  • Administered intravenously
  • Dose-limiting toxicity is QT prolongation
  • Common toxicities include fatigue, nausea, and neuropathy
  • Dangerous toxicities include QT prolongation, APL differentiation syndrome, and hepatotoxicity
• Mitotane is an adrenal cytotoxic agent that inhibits adrenal steroidogenesis and is non-specific to the cell cycle
  • Administered orally
  • Requires monitoring of adrenal insufficiency and CNS effects
  • Dose-limiting toxicity is neurotoxicity
  • Common toxicities include nausea, fatigue, and diarrhea
  • Dangerous toxicities include adrenal insufficiency, neurotoxicity, and hepatotoxicity
• Eribulin inhibits microtubule dynamics and is specific to the M phase
  • Administered intravenously
  • Requires monitoring of neuropathy and liver function
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include fatigue, neuropathy, and alopecia
  • Dangerous toxicities include myelosuppression, neurotoxicity, and hepatotoxicity
• Ixabepilone stabilizes microtubules and is specific to the M phase
  • Administered intravenously
  • Requires monitoring of neuropathy, premedicate for hypersensitivity
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include neuropathy, fatigue, and nausea
  • Dangerous toxicities include myelosuppression, neurotoxicity, and hypersensitivity
• Lenalidomide inhibits angiogenesis and enhances immunity
  • It is a immunomodulatory agent, and is non-specific to the cell cycle
  • Administered orally. Requires monitoring of blood counts and thrombosis risk
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include fatigue and rash
  • Dangerous toxicities include thrombosis and myelosuppression
• Pomalidomide inhibits angiogenesis and enhances immunity
  • It is a immunomodulatory agent, and is non-specific to the cell cycle
  • Administered orally. Requires monitoring of blood counts and thrombosis risk
  • Dose-limiting toxicity is myelosuppression
  • Common toxicities include fatigue, rash, and neuropathy
  • Dangerous toxicities include thrombosis, neurotoxicity, and infection
• Thalidomide inhibits angiogenesis and enhances immunity
  • It is a immunomodulatory agent, and is non-specific to the cell cycle
  • Administered orally. Requires monitoring of thrombosis risk, and neuropathy
  • Dose-limiting toxicity is neurotoxicity
  • Common toxicities include Fatigue, cytopenias, nausea
  • Dangerous toxicities include Thrombosis, neurotoxicity, teratogenicity